Advancements in Treatment Selection and Sequencing in HER2-Positive Metastatic Breast Cancer: Insights from ASCO 2025 - Episode 6
Panelists discuss how patient selection for trastuzumab deruxtecan–based first-line therapy should consider factors like hormone receptor status, disease burden, brain metastases, and the balance between efficacy and quality of life.
Patient Population Analysis and Treatment Selection
The DESTINY-Breast09 trial population differed from typical clinical practice, with higher proportions of de novo metastatic disease and more balanced hormone receptor status (approximately 50/50 positive/negative) compared with real-world patient populations. This international study design may limit direct applicability to US practice patterns, where different subsequent therapy access exists. Despite these differences, benefit was consistent across all prespecified subgroups with similar hazard ratios.
Patients with PIK3CA mutations showed particularly impressive benefit, which is significant given this mutation's association with more aggressive HER2-positive disease. The small subset of patients with baseline brain metastases (5-6%) also demonstrated substantial benefit, with wide confidence intervals suggesting deep clinical benefit for this high-risk population. These findings confirm prior DESTINY-Breast12 data showing T-DXd efficacy in central nervous system (CNS) disease.
Treatment selection considerations vary by hormone receptor status, with PATINA trial results offering compelling alternative for hormone receptor-positive patients showing similar progression-free survival benefits with potentially better quality of life. For patients with hormone receptor–negative disease or those requiring rapid response due to aggressive disease features, T-DXd represents an attractive first-line option. Access to T-DXd in subsequent lines remains good, providing flexibility in sequencing decisions.